Restorative Neurology and Neuroscience - Volume 36, issue 3

Authors: Zhao, Haijun | Lu, Yan | Wang, Yuan | Han, Xiaochun | Zhang, Yanan | Han, Bingbing | Wang, Tong | Li, Yan | Wang, Shijun

Article Type: Research Article

Abstract: Background: Neurological deficits is one of the most prevalent clinical manifestation after stroke. The effects of astrocytes activated by electroacupunture (EA) after stroke on the neurological recovery in middle cerebral artery occlusion (MCAO) rats was not clear and definite. Objective: Our previous study showed that treatment with EA for 7 days contributed to the activation of astrocytes in MCAO rats. The purposes of this study were to 1) confirm the effects of EA for 14 days on activation of astrocytes in MCAO rats, and 2) test the relationships between activation of astrocytes and neurological functional recovery induced by …EA in MCAO rats. Methods: All rats were randomly divided into five groups: naïve control group, sham control control group, MCAO, MCAO/EAn, MCAO/EAd (n  = 8, for each group). Rats in MCAO/EAn group received EA treatment at acupoints of Neiguan (PC06). MCAO/EAd group received EA stimulus at acupoints of Diji (SP08). The primary indicators were locomotor recovery, histopathology, immunohistochemistry, RT-PCR and Western blot. Results: The neurological deficit and histopathological improvements and activation of astrocytes were observed after EA treatment at acupoints PC06. Parametric correlation analyses revealed a cubic correlation relationship between activation of astrocytes and neurological recovery of MCAO rats treated with EA. Conclusion: EA treatment at the acupoints of Neiguan involved in the regulation of activation of astrocytes, which our data suggested has a cubic correlation relationship with the neurological recovery of MCAO rats. Show more

Keywords: EA treatment, astrocytes, functional recovery, MCAO rats

DOI: 10.3233/RNN-170722

Citation: Restorative Neurology and Neuroscience, vol. 36, no. 3, pp. 301-312, 2018

Authors: Ogourtsova, Tatiana | Archambault, Philippe S. | Lamontagne, Anouk

Article Type: Research Article

Abstract: Background: Unilateral spatial neglect (USN), a highly prevalent and disabling post-stroke deficit, has been shown to affect the recovery of locomotion. However, our current understanding of USN role in goal-directed locomotion control, and this, in different cognitive/perceptual conditions tapping into daily life demands, is limited. Objectives: To examine goal-directed locomotion abilities in individuals with and without post-stroke USN vs. healthy controls. Methods: Participants (n  = 45, n  = 15 per group) performed goal-directed locomotion trials to actual, remembered and shifting targets located 7 m away at 0° and 15° right/left while immersed in a 3-D virtual environment. …Results: Greater end-point mediolateral displacement and heading errors (end-point accuracy measures) were found for the actual and the remembered left and right targets among those with post-stroke USN compared to the two other groups (p  <  0.05). A delayed onset of reorientation to the left and right shifting targets was also observed in USN+ participants vs. the other two groups (p  <  0.05). Results on clinical near space USN assessment and walking speed explained only a third of the variance in goal-directed walking performance. Conclusion: Post-stroke USN was found to affect goal-directed locomotion in different perceptuo-cognitive conditions, both to contralesional and ipsilesional targets, demonstrating the presence of lateralized and non-lateralized deficits. Beyond neglect severity and walking capacity, other factors related to attention, executive functioning and higher-order visual perceptual abilities (e.g. optic flow perception) may account for the goal-directed walking deficits observed in post-stroke USN+. Goal-directed locomotion can be explored in the design of future VR-based evaluation and training tools for USN to improve the currently used conventional methods. Show more

Keywords: Cerebrovascular accident, hemineglect, gait, locomotion, trajectory deviation

DOI: 10.3233/RNN-170766

Citation: Restorative Neurology and Neuroscience, vol. 36, no. 3, pp. 313-331, 2018

Authors: Kesar, Trisha M. | Stinear, James W. | Wolf, Steven L.

Article Type: Research Article

Abstract: Neuroplasticity is a fundamental yet relatively unexplored process that can impact rehabilitation of lower extremity (LE) movements. Transcranial magnetic stimulation (TMS) has gained widespread application as a non-invasive brain stimulation technique for evaluating neuroplasticity of the corticospinal pathway. However, a majority of TMS studies have been performed on hand muscles, with a paucity of TMS investigations focused on LE muscles. This perspective review paper proposes that there are unique methodological challenges associated with using TMS to evaluate corticospinal excitability of lower limb muscles. The challenges include: (1) the deeper location of the LE motor homunculus; (2) difficulty with targeting individual …LE muscles during TMS; and (3) differences in corticospinal circuity controlling upper and lower limb muscles. We encourage future investigations that modify traditional methodological approaches to help address these challenges. Systematic TMS investigations are needed to determine the extent of overlap in corticomotor maps for different LE muscles. A simple, yet informative methodological solution involves simultaneous recordings from multiple LE muscles, which will provide the added benefit of observing how other relevant muscles co-vary in their responses during targeted TMS assessment directed toward a specific muscle. Furthermore, conventionally used TMS methods (e.g., determination of hot spot location and motor threshold) may need to be modified for TMS studies involving LE muscles. Additional investigations are necessary to determine the influence of testing posture as well as activation state of adjacent and distant LE muscles on TMS-elicited responses. An understanding of these challenges and solutions specific to LE TMS will improve the ability of neurorehabilitation clinicians to interpret TMS literature, and forge novel future directions for neuroscience research focused on elucidating neuroplasticity processes underlying locomotion and gait training. Show more

Keywords: Neuroplasticity, non-invasive brain stimulation, leg muscles, homunculus, motor cortex, gait, posture

DOI: 10.3233/RNN-170801

Citation: Restorative Neurology and Neuroscience, vol. 36, no. 3, pp. 333-348, 2018

Authors: Hicks, Jarrod M. | Taub, Edward | Womble, Brent | Barghi, Ameen | Rickards, Tyler | Mark, Victor W. | Uswatte, Gitendra

Article Type: Research Article

Abstract: Background: Infarct size and location account for only a relatively small portion of post-stroke motor impairment, suggesting that other less obvious factors may be involved. Objective: Examine the relationship between white matter hyperintensity (WMH) load among other factors and upper extremity motor deficit in patients with mild to moderate chronic stroke. Methods: The magnetic resonance images of 28 patients were studied. WMH load was assessed as total WMH volume and WMH overlap with the corticospinal tract in the centrum semiovale. Hemiparetic arm function was measured using the Motor Activity Log (MAL) and Wolf Motor Function Test …(WMFT). Results: Hierarchical multiple regression models found WMH volume predicted motor deficits in both real-world arm use (MAL;ΔR2  = 0.12, F(1, 22) = 4.73, p  = 0.04) and in arm motor capacity as measured by a laboratory motor function test (WMFT;ΔR2  = 0.18, F(1, 22) = 6.32, p  = 0.02) over and above age and lesion characteristics. However, these models accounted for less than half of the variance in post-stroke motor deficits. Conclusion: The results suggest that WMH may be an important factor to consider in stroke-related upper extremity motor impairment. Nonetheless, the basis of the largest part of the post-stroke motor deficit remains unaccounted for by structural CNS factors. This component may be behavioral or learned, involving learned nonuse. Show more

Keywords: Stroke, white matter hyperintensities, motor deficits, MRI, upper extremity, hemiparesis

DOI: 10.3233/RNN-170746

Citation: Restorative Neurology and Neuroscience, vol. 36, no. 3, pp. 349-357, 2018

Authors: Nenert, Rodolphe | Allendorfer, Jane B. | Martin, Amber M. | Banks, Christi | Vannest, Jennifer | Holland, Scott K. | Hart, Kimberly W. | Lindsell, Christopher J. | Szaflarski, Jerzy P.

Article Type: Research Article

Abstract: Background: Recovery from stroke-induced aphasia is typically protracted and involves complex functional reorganization. The relative contributions of the lesioned and non-lesioned hemispheres to this process have been examined in several cross-sectional studies but longitudinal studies involving several time-points and large numbers of subjects are scarce. Objective: The aim of this study was to address the gaps in the literature by longitudinally studying the evolution of post-stroke lateralization and localization of language-related fMRI activation in the first year after single left hemispheric ischemic stroke. Method: Seventeen patients with stroke-induced aphasia were enrolled to undergo detailed behavioral testing …and fMRI at 2, 6, 12, 26, and 52 weeks post-stroke. Matched for age, handedness and sex participants were also enrolled to visualize canonical language regions. Results: Behavioral results showed improvements over time for all but one of the behavioral scores (Semantic Fluency Test). FMRI results showed that the left temporal area participates in compensation for language deficits in the first year after stroke, that there is a correlation between behavioral improvement and the left cerebellar activation over time, and that there is a shift towards stronger frontal left-lateralization of the fMRI activation over the first year post-stroke. Temporary compensation observed in the initial phases of post-stroke recovery that involves the non-lesioned hemisphere may not be as important as previously postulated, since in this study the recovery was driven by activations in the left fronto-temporal regions. Conclusion: Language recovery after left hemispheric ischemic stroke is likely driven by the previously involved in language and attention left hemispheric networks. Show more

Keywords: Stroke, recovery, language, aphasia, MRI, longitudinal

DOI: 10.3233/RNN-170767

Citation: Restorative Neurology and Neuroscience, vol. 36, no. 3, pp. 359-385, 2018

Authors: Venkatachalam, Sankar | Neelamegan, Sridharan | Okuda, Tetsuhito | Marcus, Akiva | Woodbury, Dale | Grumet, Martin

Article Type: Research Article

Abstract: Objective: Mesenchymal stem/stromal cells (MSC) promote recovery after spinal cord injury (SCI) using adult bone marrow MSC (BM-MSC). Newborn tissues are a convenient source of MSC that does not involve an invasive procedure for cell collection. In this study the authors tested the effects of rat amnion MSC clone (rAM-MSC) in SCI. Methods: We tested intra-parenchymal injection of a GFP+ rat rAM-MSC clone derived from E18.5 rats in rat SCI and measured behavioral recovery (BBB scores), histology and X-ray opacity. Expression of aggrecan was measured in culture after treatment with TGFß. Results: Injection of rAM-MSC after …SCI did not improve BBB scores compared to control vehicle injections; rather they reduced scores significantly over 6 weeks. Spinal cords injected with rAM-MSC were hard in regions surrounding the SCI site, which was confirmed by X-ray opacity. Whole mount imaging of these cords showed minimal tissue loss in the SCI site that occurred in SCI controls, and persistence of GFP+ rAM-MSC. Mason’s Trichrome staining of tissue sections showed more intense staining for extracellular matrix (ECM) surrounding and extending beyond the SCI site with injections of rAM-MSC but not in controls. In response to TGF-ß treatment in culture, chondrogenic aggrecan was expressed at higher levels in rAM-MSC than in rBM-MSC, suggesting that the upregulation of TGF-ß in SCI sites may promote chondrogenic differentiation. Conclusion: Acute injection after SCI of a clonally expanded rAM-MSC resulted in aberrant differentiation towards a chondrocytic phenotype that disrupts the spinal cord and inhibits behavioral recovery after SCI. It will be critical to ensure that injection of extensively expanded neonatal cells do not differentiate aberrantly in traumatic CNS tissue and disrupt recovery. Show more

Keywords: Spinal cord injury, amnion, mesenchymal, ECM, differentiation

DOI: 10.3233/RNN-170786

Citation: Restorative Neurology and Neuroscience, vol. 36, no. 3, pp. 387-396, 2018

Authors: Rink, Svenja | Bendella, Habib | Alsolivany, Kurdin | Meyer, Carolin | Woehler, Aliona | Jansen, Ramona | Isik, Zeynep | Stein, Gregor | Wennmachers, Sina | Nakamura, Makoto | Angelov, Doychin N.

Article Type: Research Article

Abstract: Background: We compared functional, electrophysiological and morphological parameters after SCI in two groups of rats Sprague Dawley (SD) rats with normal vision and blind rats from a SD-substrain “Royal College of Surgeons” (SD/RCS) who lose their photoreceptor cells after birth due to a genetic defect in the retinal pigment epithelium. For these animals skin-, intramuscular-, and tendon receptors are major available means to resolve spatial information. Objective: The purpose of this study was to check whether increased sensitivity in SD/RCS rats would promote an improved recovery after SCI. Methods: All rats were subjected to severe compression …of the spinal cord at vertebra Th8, spinal cord segment Th10. Recovery of locomotion was analyzed at 1, 3, 6, 9, and 12 weeks after SCI using video recordings of beam walking and inclined ladder climbing. Five functional parameters were studied: foot-stepping angle (FSA), rump-height index (RHI) estimating paw placement and body weight support, respectively, number of correct ladder steps (CLS) assessing skilled hindlimb movements, the BBB-locomotor score and an established urinary bladder score (BS). Sensitivity tests were followed by electrophysiological measurement of M- and H-wave amplitudes from contractions of the plantar musculature after stimulation of the tibial nerve. The closing morphological measurements included lesion volume and expression of astro- and microglia below the lesion. Results: Numerical assessments of BBB, FSA, BS, lesion volume and GFAP-expression revealed no significant differences between both strains. However, compared to SD-rats, the blind SD/RCS animals significantly improved RHI and CLS by 6 – 12 weeks after SCI. To our surprise the withdrawal latencies in the blind SD/RCS rats were longer and the amplitudes of M- and H-waves lower. The expression of IBA1-immunoreactivity in the lumbar enlargement was lower than in the SD-animals. Conclusion: The longer withdrawal latencies suggest a decreased sensitivity in the blind SD/RCS rats, which promotes better recovery after SCI. In this way our results provide indirect support to earlier work showing, that hypersensitivity and chronic pain after contusive SCI impair the recovery of locomotor function. Show more

Keywords: Compression spinal cord injury, blind SD/RCS rats, recovery of motor performance, functional parameters, electrophysiological measurements

DOI: 10.3233/RNN-170789

Citation: Restorative Neurology and Neuroscience, vol. 36, no. 3, pp. 397-416, 2018

Authors: Setter, Deborah O. | Haulcomb, Melissa M. | Beahrs, Taylor | Meadows, Rena M. | Schartz, Nicole D. | Custer, Sara K. | Sanders, Virginia M. | Jones, Kathryn J.

Article Type: Research Article

Abstract: Background: When nerve transection is performed on adult rodents, a substantial population of neurons survives short-term disconnection from target, and the immune system supports this neuronal survival, however long-term survival remains unknown. Understanding the effects of permanent axotomy on cell body survival is important as target disconnection is the first pathological occurrence in fatal motoneuron diseases such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). Objective: The goal of this study was to determine if facial motoneurons (FMN) could survive permanent target disconnection up to 26 weeks post-operation (wpo) after facial nerve axotomy (FNA). In addition, …the potentially additive effects of immunodeficiency and motoneuron disease on post-axotomy FMN survival were examined. Methods: This study included three wild type (WT) mouse strains (C57BL/6J, B6SJL, and FVB/NJ) and three experimental models (RAG-2–/– : immunodeficiency; mSOD1: ALS; Smn –/– /SMN2+/+ : SMA). All animals received a unilateral FNA, and FMN survival was quantified at early and extended post-operative timepoints. Results: In the C57BL/6J WT group, FMN survival significantly decreased at 10 wpo (55±6%), and then remained stable out to 26 wpo (47±6%). In the RAG-2–/– and mSOD1 groups, FMN death occurred much earlier at 4 wpo, and survival plateaued at approximately 50% at 10 wpo. The SMA model and other WT strains also exhibited approximately 50% FMN survival after FNA. Conclusion: These results indicate that immunodeficiency and motoneuron disease accelerate axotomy-induced neuron death, but do not increase total neuron death in the context of permanent target disconnection. This consistent finding of a target disconnection-resilient motoneuron population is prevalent in other peripheral nerve injury models and in neurodegenerative disease models as well. Characterization of the distinct populations of vulnerable and resilient motoneurons may reveal new therapeutic approaches for injury and disease. Show more

Keywords: Motoneuron, axotomy, amyotrophic lateral sclerosis, spinal muscular atrophy, neuron survival, peripheral nerve injury, motor neuron

DOI: 10.3233/RNN-170809

Citation: Restorative Neurology and Neuroscience, vol. 36, no. 3, pp. 417-422, 2018

Authors: Tolahunase, Madhuri R. | Sagar, Rajesh | Faiq, Muneeb | Dada, Rima

Article Type: Research Article

Abstract: Background: Current interventions for major depressive disorder (MDD) are suboptimal, and only one third respond to them on initial treatment. Neuroplasticity theories are the basis for several emerging treatments. Evidence on the impact of yoga, a well-known mind-body intervention, on neuroplasticity in MDD is limited. Objectives: To determine the effects of 12-week yoga- and meditation-based lifestyle intervention (YMLI) on depression severity and systemic biomarkers of neuroplasticity in adult MDD patients on routine drug treatment. Methods: A total of 58 MDD patients were randomized into yoga or control group. The severity of depression was assessed with Beck …Depression Inventory-II scale (BDI-II). Blood samples were collected before and after intervention for the measurement of the biomarkers that characterize neuroplasticity, including mind-body communicative and cellular health biomarkers. Results: There was a significant decrease [difference between means, (95% CI)] in BDI-II score [–5.83 (–7.27, –4.39), p  < 0.001] and significant increase in BDNF (ng/ml) [5.48 (3.50, 7.46), p  < 0.001] after YMLI compared to control group. YMLI significantly increased DHEAS, sirtuin 1, and telomerase activity levels, and decreased cortisol, and IL-6 levels, in addition to decreasing DNA damage and balancing oxidative stress. Multiple regression analyses were used to associate neuroplasticity biomarkers with depression severity. A ‘post-intervention change in BDNF’ x ‘group’ interaction indicated that yoga group had more BDNF in association with less BDI-II scores relative to controls. Increased sirtuin 1 and telomerase activity and decreased cortisol significantly predicted this association (all p  < 0.05). Conclusion: These results suggest that decrease in depression severity after YMLI in MDD is associated with improved systemic biomarkers of neuroplasticity. Thus YMLI can be considered as a therapeutic intervention in MDD management. Show more

Keywords: Depression, Major depressive disorder, Yoga, Oxidative stress, BDNF, Sirtuin 1, Telomere

DOI: 10.3233/RNN-170810

Citation: Restorative Neurology and Neuroscience, vol. 36, no. 3, pp. 423-442, 2018